Basic MS Research can be defined as analysis of mechanism of induction, pathogenesis and regulation of neuroinflammatory demyelinating disease using in vivo and in vitro experimental models. This is an area of longstanding and growing strength for Denmark.
Whether viral infections can induce MS was addressed by seminal studies from Lars Fugger and colleagues at Oxford and Aarhus, showing encephalitogenicity of cross-reactive myelin and Epstein-Barr virus epitopes in TCR transgenic mice (1). The role of innate immunity in controlling CNS virus infection also has relevance to MS, as studied by Søren Paludan and colleagues at Aarhus University (2). Åsa Andersson at Copenhagen University studies susceptibility genes that may predispose to MS, in the animal model EAE (3).
The need to understand clinical therapies for and regulation of MS led Per Soelberg Sørensen, Finn Sellebjerg and colleagues at the Danish MS Centre to use EAE to probe mechanism of IVIg (4) and to contribute to more recent studies of regulatory T cells in MS-like neuroinflammation (5). Shohreh Izzazadeh-Navikas (BRIC, Copenhagen University) has elucidated these novel regulatory T cell subsets (5) as well as roles for type I IFN in regulating neuroinflammation in EAE (6). Trevor Owens and colleagues at University of Southern Denmark in Odense have also contributed to the latter topic, showing protection against EAE by innately-induced type I IFN in the CNS (7, 8).
Chemokine profiles are of interest in MS since they reflect and may predict immune infiltration. The Owens group characterized encephalitogenic epitope selective induction of chemokine receptor expression and CD4+ T cell cytokine subset association with chemokines and their receptors in EAE (9). Studies on cytokine and chemokine influences on virus-specific neuroinflammation by the group of Allan Randrup Thomsen and Jan Pravsgaard Christensen at the Panum Institute have increased our understanding of these processes (10, 11).
A key aspect in MS is the role of astrocytes. Studies by Schousboe and colleagues established in vitro systems for study of cellular interactions, which led to understanding of the role of NCAM and other adhesion molecules (12), and involvement of astrocytes in modulation of neurotransmitter function uptake (13), as well as elucidation of transcriptomic and metabolic profiles of protoplasmic astrocytes (14). The importance of astrocytes was shown by their removal in EAE (15).
Oligodendroglia are a primary target of immune attack in MS and their development has been studied by the labs of Bente Finsen in Odense (16, 17) and Lisbeth Laursen in Aarhus (18). The Finsen group have also identified complex interplay between encephalitogenic T cells, oligodendrocyte precursor cells and microglial cells in experimentally demyelinated CNS (19). Those studies are complemented by studies from the Owens group that show immunoregulatory properties (including type I IFN production) of microglial subsets in EAE and in other disease models (20). The role of microglia in experimental demyelination is being studied by Zsolt Illes and colleages at Odense University Hospital (21).
Communication between the central nervous system and the periphery is central to neuroimmunology. Analyses of blood-brain barrier and its permeability date back to studies by Laursen, Diemer, Gjedde and colleagues in Copenhagen (22, 23). Maiken Nedergaard’s group, based in Rochester and Copenhagen, have identified glymphatic pathways of paravascular solute transport that potentially bring brain antigens to draining lymph nodes (24). How antibody paravascularly transported from CSF mediates inside-out blood-brain breakdown has been studied by Nasrin Asgari from Vejle Hospital and colleagues in Odense, using experimental models for the MS-related disease Neuromyelitis Optica (25). Torben Moos at Aalborg University studies mechanisms for molecular and pharmacological access to the CNS, of potential relevance for therapeutic applications (26).
Basic MS research is therefore an active and expanding area in Denmark.
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